This proposal is a Competitive Revision request submitted in response to Notice Number (NOT- OD-09-058) entitled "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". Spinal manipulative therapy (SMT) is a common treatment for patients with low back pain (LBP) with evidence that it provides therapeutic benefit for some patients. Despite common usage and evidence of benefit, the mechanisms underlying the therapeutic effects of SMT are not well-understood. Current theories focus on biomechanical and neurophysiologic changes produced by SMT as possible mechanisms, but these changes have not been sufficiently studied in patients with LBP;and prior research has not examined these changes in relation to the therapeutic response to SMT. The overall goal of the original R21 grant on which this competitive renewal is based is to quantify the effects of SMT on important neurophysiologic and biomechanical variables in subjects with LBP, and relate changes occurring in neurophysiologic and biomechanical variables to the clinical outcomes of the SMT treatment. Since the original grant was submitted, further evidence has emerged in support of a neurophysiologic effect of SMT. More specifically, the high-velocity, low-amplitude impulse delivered by SMT is believed to stimulate mechanosensitive afferents in paraspinal tissues, altering input to the central nervous system, and enhancing motor neuron excitability. One muscle that appears to be facilitated by SMT is the lumbar multifidus muscle. Our original R21 grant is currently examining the impact of SMT on the multifidus muscle using ultrasound to quantify muscle activation before and after receiving SMT. Our experience appears to be in line with recent research studies indicating that SMT has an excitatory effect on the multifidus muscle, resulting in increased activation after SMT. Moving forward with research that aims to capitalize on the effect of SMT on the multifidus muscle as an opportunity to enhance the effectiveness of SMT interventions will require the use of additional outcome measures whose reliability and validity has not been adequately described in subjects with LBP. The goal of this revision request is to examine the utility of these novel outcome measures as an ancillary aim to the ongoing clinical research funded by our original R21 grant. Specifically, we propose to examine the reliability and concurrent validity of the use of magnetic resonance imaging (MRI) to quantify cross-sectional area and fat infiltration of the multifidus muscle in individuals with LBP. Once established, these methods can be used as outcome measures in subsequent clinical studies to examine the impact of SMT on these important parameters. PUBLIC HEALTH RELEVANCE: Low back pain is a common condition resulting in high costs and disability. Manipulation is a treatment frequently used to treat low back pain, and although some individuals benefit from the treatment, why manipulation works is presently not known. One theory is that manipulation changes recruitment of the multifidus muscle. We will examine the ability to measure changes in the multifidus muscle and examine the relationship between changes and back pain symptoms to help determine the relevance of changes found in the multifidus muscle and establish procedures for future studies examining the effects of manipulation.